Using Tandem LC-MS for Cleaning Validation

Within any pharmaceutical manufacturing facility it is crucial to ensure that following the manufacture of a product, equipment has been thoroughly cleaned to avoid risks of any carry over into the following product. The process by which this is achieved is called cleaning validation, and an approach for conducting such validations is to develop a sequence of operations likely requiring the application of solvents or detergents and rinses. It must be demonstrated that this sequence of operations can remove traces of product residues down to levels that do not present risks to patients that may receive them as carryover components in the next product manufactured on the same equipment train. To collect data, swab samples taken from equipment surfaces or rinsates (i.e., washes that are used for the rinsing out of equipment after they have been treated with detergent) are analyzed. Typically, samples of the final washes are taken for analysis.

If a validated cleaning procedure has not been developed, it will be expected that swab or rinsate analyses will be conducted on each occasion to demonstrate effectiveness of the cleaning procedure; this practice is referred to as cleaning verification.

For both cleaning validations and verifications, analytical testing of samples is a crucial step. Typically, analytical procedures that are specific for the APIs that were used for the manufacturing of previous products are applied. It is expected that a separate analytical procedure will be developed and validated for each individual API that is handled in any manufacturing facility. High-performance liquid chromatography (HPLC) is probably the most widely used analytical procedure for this application with ultra-high performance liquid chromatography (UHPLC) gaining increasing popularity, but liquid chromatography-mass spectrometry (LC-MS) also offers potential opportunities.